It has been generally assumed that secretin is a physiological stimulant for pancreatic water and bicarbonate secretion. There is, however, no proof for this assumption. In fact, there is some recent evidence that it may be invalid. In order to qualify as physiologic stimulant, secretin has to be released after intake of a meal. Using a radioimmunoassay which increased sensitivity (6 pg/ml) and determining IRS concentrations in peripheral and portal venous serum we plan to investigate whether or not secretin is released after a meal in dogs and in human subjects. Existence of molecular heterogeneity has recently been demonstrated for secretin. In this study, we plan to separate different forms of secretin immunoreactivity by Sephadex Gel Filtration and by polyacrylamide gel electrophoresis and to study their physicochemical and immunochemical characteristics, their metabolic half-life and their biological activity. There is some evidence to suggest that ectopic secretin production by tumors exist in humans. We hope to obtain information on the incidence of ectopic secretin secretion, on the kind of tumor it is most frequently associated with and whether or not it is associated with a clinical syndrome by determining the secretin content in extracts obtained from solid tumors. Somatostatin may have therapeutic potential in insulin requiring diabetics, treatment of diabetic ketoacidosis, acromegaly and the Zollinger-Ellison syndrome. However, the tetradecapeptide also has serious unwanted side effects. We have recently demonstrated that somatostatin inhibits HCl stimulated release of secretin and pancreatic secretion of bicarbonate and enzymes. In this study we plan to investigate whether or not meal stimulated pancreatic exocrine secretion is similarly affected by somatostatin.